Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr;43(2):375-386.
doi: 10.1007/s10930-023-10161-1. Epub 2023 Oct 4.

Kennedy Epitope (KE)-dependent Retrograde Transport of Efficiently Cleaved HIV-1 Envelopes (Envs) and its Effect on Env Cell Surface Expression and Viral Particle Formation

Supratik Das  1   2 , Hilal Ahmad Parray #  3 , Adarsh Kumar Chiranjivi #  3 , Prince Kumar  3 , Abhishek Goswami  3 , Manish Bansal  4 , Deepak Kumar Rathore  3 , Rajesh Kumar  5 , Sweety Samal  3
Affiliations

Kennedy Epitope (KE)-dependent Retrograde Transport of Efficiently Cleaved HIV-1 Envelopes (Envs) and its Effect on Env Cell Surface Expression and Viral Particle Formation

Supratik Das et al. Protein J. 2024 Apr.

Erratum in

Abstract

Efficiently cleaved HIV-1 Envs are the closest mimics of functional Envs as they specifically expose only bNAb (broadly neutralizing antibody) epitopes and not non-neutralizing ones, making them suitable for developing vaccine immunogens. We have previously identified several efficiently cleaved Envs from clades A, B, C and B/C. We also described that truncation of the CT (C-terminal tail) of a subset of these Envs, but not others, impairs their ectodomain conformation/antigenicity on the cell surface in a CT conserved hydrophilic domain (CHD) or Kennedy epitope (KE)-dependent manner. Here, we report that those Envs (4 - 2.J41 and JRCSF), whose native-like ectodomain conformation/antigenicity on the cell surface is disrupted upon CT truncation, but not other Envs like JRFL, whose CT truncation does not have an effect on ectodomain integrity on the cell surface, are also defective in retrograde transport from early to late endosomes. Restoration of the CHD/KE in the CT of these Envs restores wild-type levels of distribution between early and late endosomes. In the presence of retrograde transport inhibitor Retro 2, cell surface expression of 4 - 2.J41 and JRCSF Envs increases [as does in the presence of Rab7a DN and Rab7b DN (DN: dominant negative)] but particle formation decreases for 4 - 2.J41 and JRCSF Env pseudotyped viruses. Our results show for the first time a correlation between CT-dependent, CHD/KE regulated retrograde transport and cell surface expression/viral particle formation of these efficiently cleaved Envs. Based on our results we hypothesize that a subset of these efficiently cleaved Envs use a CT-dependent, CHD/KE-mediated mechanism for assembly and release from late endosomes.

Keywords: C-terminal tail; Efficiently cleaved; Envelope; HIV-1; Kennedy epitope; Retrograde transport.

PubMed Disclaimer

Similar articles

See all similar articles

References

    1. Li Y, Migueles SA, Welcher B, Svehla K, Phogat A et al (2007) Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat Med 13:1032–1034 - PubMed - PMC - DOI
    1. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P et al (2009) Broad and potent neutralizing antibodies from an african donor reveal a new HIV-1 vaccine target. Science 326:285–289 - PubMed - PMC - DOI
    1. Sather DN, Stamatatos L (2010) Epitope specificities of broadly neutralizing plasmas from HIV-1 infected subjects. Vaccine 28(Suppl 2):B8–12 - PubMed - DOI
    1. Moore PL, Gray ES, Sheward D, Madiga M, Ranchobe N et al (2011) Potent and broad neutralization of HIV-1 subtype C by plasma antibodies targeting a quaternary epitope including residues in the V2 loop. J Virol 85:3128–3141 - PubMed - PMC - DOI
    1. Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F et al (2011) Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333:1633–1637 - PubMed - PMC - DOI

Publication types

MeSH terms

Substances

LinkOut - more resources